In recent years, cancer mortality in our country has clearly been on the rise. People's lives and the quality of life are seriously threatened by cancer. Thus, it is a challenging and significant subject to search for new anticancer drugs with high efficacy and low toxicity in the life sciences nowadays. Receptor tyrosine kinase is a kind of transmembrane protein involved in signal transduction. It has been shown that over 50% of the proto-oncogene and oncogene products have tyrosine kinase activity, and their abnormal expression causes tumorigenesis. Tyrosine kinase inhibitors have been approved to be on the market since 2001, which have become a new class of anticancer drugs with good performance.
Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family. The epidermal growth factor receptor pathway plays a very important role in tumorigenesis and progression, which has become the main research subject and one of the developing targets in the field of cancer therapy. Such drugs which have been on the market now include erlotinib, gefitinib and lapatinib (Tykerb, GW572016), as well as neratinib, which is currently in the clinical phase. PCT Patent Application Publication WO2011029265 discloses a method for the preparation of the compound (R, E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquino line-6-yl)-3-(1-methylpyrrolidino-2-yl)acrylamide (referred to as “SHR1258” below for convenience). This drug molecule has distinct advantages of pharmacokinetics and pharmacodynamics. Although PCT Patent Application Publication WO2011029265 discloses the chemical structure and preparation method of compound SHR1258, it is silent to the condition of its salification. In Chinese Patent Application No. 201110062359.8, the dimaleate of this compound (referred to as “SHR1258 dimaleate” below) has been described, and its structure is as follows:

However, the inventors did not do further research on the polymorphs and preparation method of SHR1258 dimaleate. As known to the person skilled in the art, the polymorph structure of the pharmaceutically active ingredient always affects the chemical stability of the drug. Different storage conditions and crystallization conditions may lead to a change in the polymorph structure of the compound, which is sometimes accompanied by other forms of polymorph. In general, an amorphous drug product does not have a regular crystal structure, and often has other defects such as poor product stability, smaller particle size, hard filtration, agglomerates easily, and poor solubility. Thus, it is necessary to improve all aspects of the nature of the above product. There is a need to search for a new polymorph which has higher polymorph purity and better chemical stability.